2025 American Academy of Neurology Abstract Website

Objective:

To determine the genetic and environmental contributions to idiopathic sensory neuropathy (ISN)

Background:

ISN is a form of peripheral neuropathy characterized by loss of sensation, numbness, tingling, and pain. Estimates of sensory neuropathy in the general population range from 1% to 3%. The cause of ISN is thought to be related to age, genetics, and environmental factors.

Design/Methods:

97 patients with ISN enrolled at the neuromuscular clinic of the University of Washington Medical Center and its affiliated Veterans Affairs Health Care Center. The patients were predominantly male (64%) with an age range of 23 to 79. Next generation sequencing of 81 genes in an inherited neuropathy panel was performed on each participant. Each subject was also queried for environmental exposures, including military history, Agent Orange exposure, occupational exposures, and heavy metal exposure.

Results:

4% of participants were shown to have a pathogenic variant. Five participants were heterozygous for variants in genes encoding for sodium channel subunits, SCN9A, SCN10A, and SCN11A. 56% of participants had previously used home pesticide products, and 25% were exposed to heavy metals. 49% of participants were members of the military, and 15% of those participants with a military background had previous exposure to Agent Orange.

We will report a factor analysis of mixed data to study associations between genetic mutations, environmental exposure factors, and demographics.

Conclusions:

In our cohort of subjects with ISN, few pathogenic mutations and variants of unknown significance were found but at lower rates than previously described in SCN genes found in other studies. More than half of the participants were exposed to home pesticides, while a minority of patients were exposed to Agent Orange or heavy metals. This suggests that the contribution of genetic and environmental factors in ISN is complex and multifactorial.